ID CBPC6_HUMAN Reviewed; 503 AA. AC Q5VU57; B3KT26; B4DG37; DT 17-APR-2007, integrated into UniProtKB/Swiss-Prot. DT 11-JAN-2011, sequence version 3. DT 16-JAN-2019, entry version 114. DE RecName: Full=Cytosolic carboxypeptidase 6; DE EC=3.4.17.-; DE AltName: Full=ATP/GTP-binding protein-like 4; GN Name=AGBL4; Synonyms=CCP6; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). RC TISSUE=Amygdala, and Brain; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16710414; DOI=10.1038/nature04727; RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., RA Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., RA Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., RA McDonald L., Evans R., Phillips K., Atkinson A., Cooper R., Jones C., RA Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., RA Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., RA Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., RA Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., RA Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., RA Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., RA Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., RA Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., RA Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., RA Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., RA Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., RA Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., RA Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., RA Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., RA Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., RA Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., RA Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., RA Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., RA Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., RA Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., RA Beck S., Rogers J., Bentley D.R.; RT "The DNA sequence and biological annotation of human chromosome 1."; RL Nature 441:315-321(2006). RN [3] RP SUBCELLULAR LOCATION. RX PubMed=23085998; DOI=10.1096/fj.12-209080; RA Rodriguez de la Vega Otazo M., Lorenzo J., Tort O., Aviles F.X., RA Bautista J.M.; RT "Functional segregation and emerging role of cilia-related cytosolic RT carboxypeptidases (CCPs)."; RL FASEB J. 27:424-431(2013). CC -!- FUNCTION: Metallocarboxypeptidase that mediates deglutamylation of CC target proteins. Catalyzes the deglutamylation of polyglutamate CC side chains generated by post-translational polyglutamylation in CC proteins such as tubulins. Also removes polyglutamates from the CC carboxy-terminus of target proteins such as MYLK. Mediates CC deglutamylation of CGAS, regulating the antiviral activity of CC CGAS. Acts as a long-chain deglutamylase and specifically shortens CC long polyglutamate chains, while it is not able to remove the CC branching point glutamate, a process catalyzed by AGBL5/CCP5. CC {ECO:0000250|UniProtKB:Q09LZ8}. CC -!- COFACTOR: CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; CC Evidence={ECO:0000250|UniProtKB:P00730}; CC Note=Binds 1 zinc ion per subunit. {ECO:0000250|UniProtKB:P00730}; CC -!- SUBUNIT: Interacts with MYLK. {ECO:0000250}. CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol CC {ECO:0000250|UniProtKB:Q09LZ8}. Cytoplasm, cytoskeleton, CC microtubule organizing center, centrosome, centriole CC {ECO:0000269|PubMed:23085998}. Golgi apparatus CC {ECO:0000269|PubMed:23085998}. Cytoplasm, cytoskeleton, cilium CC basal body {ECO:0000269|PubMed:23085998}. Note=Colocalizes with CC gamma-tubulin in the centrioles at interphase and dividing cells CC and with glutamylated tubulin in basal bodies of ciliated cells. CC {ECO:0000269|PubMed:23085998}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q5VU57-1; Sequence=Displayed; CC Name=2; CC IsoId=Q5VU57-2; Sequence=VSP_040435, VSP_040436; CC Note=No experimental confirmation available.; CC -!- SIMILARITY: Belongs to the peptidase M14 family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=BAG52938.1; Type=Frameshift; Positions=501; Evidence={ECO:0000305}; CC Sequence=BAG57648.1; Type=Frameshift; Positions=501; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AK094826; BAG52938.1; ALT_FRAME; mRNA. DR EMBL; AK294394; BAG57648.1; ALT_FRAME; mRNA. DR EMBL; AC099788; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL355809; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL390023; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL391844; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL590432; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL591602; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL645507; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL645730; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR CCDS; CCDS44137.1; -. [Q5VU57-1] DR RefSeq; NP_001310502.1; NM_001323573.1. [Q5VU57-2] DR RefSeq; NP_116174.3; NM_032785.3. [Q5VU57-1] DR UniGene; Hs.551844; -. DR UniGene; Hs.679809; -. DR ProteinModelPortal; Q5VU57; -. DR STRING; 9606.ENSP00000360905; -. DR MEROPS; M14.027; -. DR iPTMnet; Q5VU57; -. DR PhosphoSitePlus; Q5VU57; -. DR BioMuta; AGBL4; -. DR DMDM; 317373463; -. DR EPD; Q5VU57; -. DR PaxDb; Q5VU57; -. DR PeptideAtlas; Q5VU57; -. DR PRIDE; Q5VU57; -. DR ProteomicsDB; 65385; -. DR ProteomicsDB; 65386; -. [Q5VU57-2] DR DNASU; 84871; -. DR Ensembl; ENST00000371839; ENSP00000360905; ENSG00000186094. [Q5VU57-1] DR GeneID; 84871; -. DR KEGG; hsa:84871; -. DR UCSC; uc001cru.3; human. [Q5VU57-1] DR CTD; 84871; -. DR DisGeNET; 84871; -. DR EuPathDB; HostDB:ENSG00000186094.16; -. DR GeneCards; AGBL4; -. DR HGNC; HGNC:25892; AGBL4. DR HPA; HPA037994; -. DR MIM; 616476; gene. DR neXtProt; NX_Q5VU57; -. DR OpenTargets; ENSG00000186094; -. DR PharmGKB; PA142672636; -. DR eggNOG; KOG3641; Eukaryota. DR eggNOG; COG2866; LUCA. DR GeneTree; ENSGT00940000155042; -. DR HOGENOM; HOG000231164; -. DR HOVERGEN; HBG107588; -. DR InParanoid; Q5VU57; -. DR OMA; KWQRIPR; -. DR OrthoDB; 481670at2759; -. DR PhylomeDB; Q5VU57; -. DR TreeFam; TF333009; -. DR Reactome; R-HSA-8955332; Carboxyterminal post-translational modifications of tubulin. DR ChiTaRS; AGBL4; human. DR GenomeRNAi; 84871; -. DR PRO; PR:Q5VU57; -. DR Proteomes; UP000005640; Chromosome 1. DR Bgee; ENSG00000186094; Expressed in 92 organ(s), highest expression level in amniotic fluid. DR CleanEx; HS_AGBL4; -. DR ExpressionAtlas; Q5VU57; baseline and differential. DR GO; GO:0005814; C:centriole; IDA:UniProtKB. DR GO; GO:0036064; C:ciliary basal body; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; ISS:UniProtKB. DR GO; GO:0005794; C:Golgi apparatus; IDA:UniProtKB. DR GO; GO:0004181; F:metallocarboxypeptidase activity; ISS:UniProtKB. DR GO; GO:0015631; F:tubulin binding; ISS:UniProtKB. DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro. DR GO; GO:0035609; P:C-terminal protein deglutamylation; ISS:UniProtKB. DR GO; GO:0051607; P:defense response to virus; ISS:UniProtKB. DR GO; GO:0035608; P:protein deglutamylation; ISS:UniProtKB. DR GO; GO:0035610; P:protein side chain deglutamylation; ISS:UniProtKB. DR InterPro; IPR000834; Peptidase_M14. DR Pfam; PF00246; Peptidase_M14; 1. DR SMART; SM00631; Zn_pept; 1. PE 2: Evidence at transcript level; KW Alternative splicing; Carboxypeptidase; Cell projection; KW Complete proteome; Cytoplasm; Cytoskeleton; Golgi apparatus; KW Hydrolase; Metal-binding; Metalloprotease; Polymorphism; Protease; KW Reference proteome; Zinc. FT CHAIN 1 503 Cytosolic carboxypeptidase 6. FT /FTId=PRO_0000284835. FT ACT_SITE 280 280 Nucleophile. FT {ECO:0000250|UniProtKB:P00730}. FT METAL 230 230 Zinc. {ECO:0000250|UniProtKB:Q09M02}. FT METAL 233 233 Zinc. {ECO:0000250|UniProtKB:Q09M02}. FT METAL 328 328 Zinc. {ECO:0000250|UniProtKB:P00730}. FT VAR_SEQ 94 94 Q -> QVREIVDTFRVVL (in isoform 2). FT {ECO:0000303|PubMed:14702039}. FT /FTId=VSP_040435. FT VAR_SEQ 455 463 Missing (in isoform 2). FT {ECO:0000303|PubMed:14702039}. FT /FTId=VSP_040436. FT VARIANT 443 443 V -> M (in dbSNP:rs60977321). FT /FTId=VAR_061078. FT CONFLICT 237 237 S -> L (in Ref. 1; BAG57648). FT {ECO:0000305}. FT CONFLICT 490 490 K -> R (in Ref. 1; BAG57648). FT {ECO:0000305}. SQ SEQUENCE 503 AA; 58230 MW; 4D1AD20229664D90 CRC64; MAEGSQSAPE AGNDMGNDDA IGGNVSKYIV LPTGYCGQPK KGHLIFDACF ESGNLGRVDQ VSEFEYDLFI RPDTCNPRFR VWFNFTVENV KESQRVIFNI VNFSKTKSLY RDGMAPMVKS TSRPKWQRLP PKNVYYYRCP DHRKNYVMSF AFCFDREEDI YQFAYCYPYT YTRFQHYLDS LQKRNMDYFF REQLGQSVQQ RKLDLLTITS PDNLREGAEQ KVVFITGRVH PGETPSSFVC QGIIDFLVSQ HPIACVLREY LVFKIAPMLN PDGVYLGNYR CSLMGFDLNR HWLDPSPWVH PTLHGVKQLI VQMYNDPKTS LEFYIDIHAH STMMNGFMYG NIFEDEERFQ RQAIFPKLLC QNAEDFSYSS TSFNRDAVKA GTGRRFLGGL LDHTSYCYTL EVSFYSYIIS GTTAAVPYTE EAYMKLGRNV ARTFLDYYRL NPVVEKVAIP MPRLRNKEIE VQRRKEKSPP YKHPLLRGPA SNYPNSKGDK KSSVNHKDPS TPF //